Heterogeneous catalysts currently dominate the field of large-scale industrial chemical synthesis, as the catalyst can easily be separated and reused after the reaction is complete. Homogeneous catalysts typically operate at milder temperatures and can exhibit activities and selectivities unknown by their heterogeneous counterparts, although problems associated with the separation, recovery and re-use of typically highly expensive homogeneous catalysts can sometimes be a limitation. Homogeneous catalysis is, however, widely used in specialty applications, such as production of pharmaceuticals, where high selectivity is of great importance.
Rapid developments in the field of catalysis are leading to an increased demand for tailor-made catalysis. Significant research efforts have been focused upon the immobilization of the organometallic species responsible for catalysis. There have been many reports of xe2x80x9cheterogenizationxe2x80x9d of homogeneous catalysts by tethering them to solid supports such as silica, alumina, polystyrene and water-soluble polymers. The act of supporting these catalysts on a heterogeneous substrate often has a deleterious effect upon their performance and, at best, the performance of such heterogeneous catalysts only approximates those of their homogeneous counterparts. Another disadvantage of supported catalysts is the continuous loss of the metal (leaching) which both contaminates the product phase and increases the production cost due to loss of expensive catalyst.
Other research efforts have. been directed to the immobilization of a catalyst in a xe2x80x9cmobile phasexe2x80x9d such as an aqueous solution immiscible with the product phase. This type of system represents an almost ideal combination of homogeneous and heterogeneous catalysis. Compared to a solid-supported catalyst, it should function more like a homogeneous catalyst and show characteristic features of a homogeneous catalyst, such as higher reactivity, higher selectivity and better reproducibility under mild conditions. This approach has been used in aqueous two-phase catalysis with water-soluble catalyst complexes bearing water-soluble ligands such as sulfonated triarylphosphines (see, for example, U.S. Pat. No. 4,248,802 by Kuntz for catalytic hydroformylation of olefins). The reactants can be either soluble in the water phase or, since the number of water-soluble organic substrates are limited, form a separate phase. The reaction can take place across the interface, in the water phase or in the dense fluid phase depending upon the hydrophilicity of the reactants. The reaction rates are then governed by the solubility of the reactant in the water, and due to decreased solubility, reaction rates are often slower than a single-phase homogeneous reaction. If the product is not water-soluble, it can be easily separated from the water-soluble catalyst complex, allowing the catalyst complex to be recycled.
Current industrial applications of water-soluble catalysts are generally limited to substrates with significant water solubility. The well-known Rhone-Poulenc process for hydroformylation of propene to butanal on a scale of around 330,000 tons per year takes advantage of a water-soluble catalyst. That process cannot be effectively extended to longer chain olefins due to their negligible solubility in water. Mass transport limitations for longer chain olefins across a phase boundary lead to significantly lower reaction rates. The ability to use water-soluble catalysts with hydrophobic or poorly water-soluble substrates remains a major challenge, not only in the hydroformylation of longer chain olefins, but also in catalytic transformations of hydrophobic substrates in general.
A number of investigators have tried to overcome the mass transfer limitations of a two-phase system by addition of either a phase transfer catalyst (PTC) or an interfacially active amphiphilic surfactant. In the case of a PTC (typically a quaternary ammonium compound), a complex is generally formed between the PTC and either (a) the catalyst in the aqueous phase whereafter the catalyst can be transported into the organic phase, or (b) the hydrophobic compound whereafter the hydrophobic compound can be transported into the aqueous phase (see Starks et al., Phase Transfer Catalysis, Chapman and Hall, New York, 1994). A major disadvantage of using a PTC is that it further complicates the purification step as the PTC is slightly soluble in both phases and cannot be easily separated into the aqueous phase for recycle.
The addition of a surfactant in a two-phase system can allow micelles of, e.g., the water phase, to be dispersed in the second phase, typically an organic phase, which significantly increases the surface area between the two phases, reaching values as high as 105 square meter per liter of microemulsion. The surfactant can also lower the surface tension between the two phases, further promoting the reaction across the interface. Although numerous studies of organic reactions have been reported in microemulsions (optically transparent microheterogeneous systems with droplet sizes from about 2 xc3x85 to about 500 xc3x85), extremely few have been reported in emulsions (milky-white opaque systems with droplet sizes greater than about 500 xc3x85), with the exception of heterogeneous polymerizations. The difficulty in breaking an emulsion or microemulsion composed of water and an organic solvent is a formidable problem. Another problem with microemulsions is that it is often necessary to add a cosolvent to achieve the proper balance of attractive and repulsive interactions on the hydrophobic and hydrophilic sides of the interface. While the cosolvent can reduce the interfacial tension between the droplets and the continuous phase, it can cause further separation problems.
Other recent approaches have been reported to overcome mass transfer limitations using organic solvents in biphasic catalysis. In one approach, Horvath et al., U.S. Pat. No. 5,463,082, describe catalysts that are soluble in fluorocarbons. Heating these systems in a fluorocarbon and hydrocarbon solvent mixture leads to a miscible homogeneous reaction mixture, which can be separated into two phases, a hydrocarbon/product phase and a fluorocarbon/catalyst phase, upon cooling after reaction.
Recently, micellar solutions of water in supercritical carbon dioxide were reported (see, Johnston et al., Science, vol. 271, pp.264, 1996). Supercritical fluids (i.e., the state of a compound when it is at or above its critical temperature and critical pressure) have liquid-to-gas like densities, higher diffusivities and lower viscosities, all due to the highly compressable nature of the fluid. There are also literature reports of using supercritical fluids, especially supercritical carbon dioxide, as solvents in homogeneous catalysis. In U.S. Pat. No. 5,198,589 by Rathke et al., cobalt carbonyl catalyzed hydroformylation was conducted in a single phase reaction medium of supercritical carbon dioxide. Carbon dioxide is an attractive alternative to organic solvents as it is environmentally benign, essentially nontoxic, inexpensive, nonflammable, has low critical conditions (Pc=73.8 bar, Tc=31xc2x0 C.) and can be easily recycled. Supercritical fluids also share many of the advantages of gases including miscibility with other gases, low viscosity, and high diffusivities, thereby providing enhanced heat transfer and the potential for faster reactions, particularly diffusion controlled reactions involving gaseous reactants such as hydrogen, oxygen and carbon monoxide. The density of the fluid, which may be adjusted with temperature and pressure, has a large effect on the solvation of the surfactant tail, and thus the phase behavior and stability of the microemulsion or emulsion. Density effects on water-in-supercritical fluid microemulsions have been explained experimentally and theoretically. The interfacial tension, (xcex3), between water and carbon dioxide (18 mNmxe2x88x921 at pressures above 70 bar) is much lower as compared to water and an organic solvent (30-50 mNmxe2x88x921). This eliminates the need of any cosolvents and also further promotes reactions across the interface. Lower xcex3 values reflect the fact that carbon dioxide is more miscible with water than typical non-polar organics, largely due to the acidity and quadrupole moment of carbon dioxide. Another important advantage of using carbon dioxide as the dispersed phase is that emulsions are easily broken by rapidly reducing the pressure, separating the water and carbon dioxide into separate phases. The carbon dioxide phase can be subsequently removed simply by vaporization. The micellar system type, i.e., microemulsion or emulsion, is governed by the type and amount of the surfactant, and the volume fractions of the water to carbon dioxide.
A catalytic system or process which overcomes these obstacles of a) separating the product from the catalyst and recycling the latter, b) decreasing mass-transfer limitations by micellar catalysis (i.e., increased surface area and decreased interfacial tension), and c) when using carbon dixoide, removal of all organic solvents for the use of environmentally benign water and carbon dioxide has now been developed using a water/dense phase fluid, e.g., carbon dioxide, micellar reaction system with the catalyst complex and reaction products each soluble in a separate phase.
It is an object of this invention to provide a process for conducting organic reactions in an aqueous biphasic reaction system employing a catalyst for a selected organic reaction, the catalyst either water-soluble or dense phase fluid-soluble and the reaction product soluble in the phase in which the catalyst is insoluble, wherein the reaction products and catalyst can be readily separated by a phase separation.
Another object of this invention is a process for conducting organic reactions in an aqueous biphasic reaction system wherein the reaction rate is enhanced by employment of an aqueous biphasic system including a water phase, a dense phase fluid, a surfactant adapted for forming an emulsion or microemulsion within said aqueous biphasic system, and a catalyst for the selected organic reaction, the catalyst comprised of a metal complex, e.g., a transition metal complex, and at least one ligand, the ligand or ligands soluble in either the water phase or the dense phase fluid.
Another object of this invention is a process for conducting organic reactions in an aqueous biphasic reaction system wherein the reaction rate is enhanced from one or more factors such as gas miscibility, lower surface tension, and increased surface area.
It is another object of this invention to provide an aqueous biphasic reaction mixture including a water phase, a dense phase fluid, and a surfactant adapted for forming an emulsion or microemulsion within said aqueous biphasic system, and a catalyst for a selected organic reaction, the catalyst comprised of a metal complex, e.g., a transition metal complex, and at least one ligand, the ligand or ligands soluble in either the water phase or the dense phase fluid.
Still another object of this invention is to provide a aqueous biphasic reaction mixture including a water phase, a dense phase fluid, and a surfactant adapted for forming an emulsion or microemulsion within said aqueous biphasic system, a catalyst for a selected organic reaction, the catalyst comprised of a metal complex, e.g., a transition metal complex, and at least one ligand, the ligand or ligands soluble in either the water phase or the dense phase fluid, and reactants for said organic reaction, the reactants soluble within one of the phases of the biphasic system.
Yet another object of the present invention is a process of conducting organic reactions such as hydroformylation reactions, hydrogenation reactions including asymmetric or enantioselective hydrogenation reactions, carbon-carbon bond forming reactions, oxidation reactions, and carbonylation reactions within an aqueous biphasic system including a water phase, a dense phase fluid, a surfactant adapted for forming an emulsion or microemulsion within said aqueous biphasic system, and a catalyst for the selected organic reaction, the catalyst comprised of a metal complex, e.g., a transition metal complex, and at least one ligand, the ligand or ligands soluble in either the water phase or the dense phase fluid.
To achieve the foregoing and other objects, and in accordance with the purposes of the present invention, as embodied and broadly described herein, the process of this invention provides for catalyzing an organic reaction to form a reaction product including placing reactants and a catalyst for the organic reaction, within an aqueous biphasic system including a water phase, a dense phase fluid, and a surfactant adapted for forming an emulsion or microemulsion of said aqueous biphasic system, the catalyst comprised of a metal complex and at least one ligand soluble within one of the phases of the aqueous biphasic system, said reactants soluble within one of the phases of said aqueous biphasic system and convertible in the presence of the catalyst to a product having low solubility within the phase of said aqueous biphasic system in which the catalyst is soluble, and maintaining said aqueous biphasic system under pressures, at temperatures, and for a period of time sufficient for said organic reaction to occur and form said reaction product, said reaction product characterized as having low solubility within the phase of said aqueous biphasic system in which the catalyst is soluble.
The present invention further provides a reaction mixture useful for carrying out an organic reaction, said mixture including an aqueous biphasic system including a water phase, a dense phase fluid,.and a surfactant adapted for forming an emulsion or microemulsion within said aqueous biphasic system; a reactant for said organic reaction, said reactant soluble within one of the phases of the biphasic system, and a catalyst for said organic reaction, said catalyst comprised of a metal complex and at least one ligand soluble within one of the phases of the aqueous biphasic system whereby the catalyst is soluble within one of the phases of the aqueous biphasic system.